RESUMO
Heart failure (HF) prognosis depends on various regulatory factors; microRNA-128 (miR-128) is identified as a regulator of cardiac fibrosis, contributing to HF. MyoD family inhibitor (MDFI), which is reported to be related with Wnt/ß-catenin pathway, is supposed to be regulated by miR-128. This study investigates the interaction between miR-128 and MDFI in cardiomyocyte development and elucidates its role in heart injury. Gene expression profiling assessed miR-128's effect on MDFI expression in HF using qPCR and Western blot analysis. Luciferase assays studied the direct interaction between miR-128 and MDFI. MTT, transwell, and immunohistochemistry evaluated the effects of miR-128 and MDFI on myocardial cells in mice HF. Genescan and luciferase assays validated the interaction between miR-128 and MDFI sequences. miR-128 mimics significantly reduced MDFI expression at mRNA and protein levels with decrease rate of 55%. Overexpression of miR-128 promoted apoptosis with the increase rate 65% and attenuated cardiomyocyte proliferation, while MDFI upregulation significantly enhanced proliferation. Elevated miR-128 levels upregulated Wnt1 and ß-catenin expression, whereas increased MDFI levels inhibited these expressions. Histological analysis with haematoxylin and eosin staining revealed that miR-128 absorption reduced MDFI expression, hindering cell proliferation and cardiac repair, with echocardiography showing corresponding improvements in cardiac function. Our findings suggest miR-128 interacts with MDFI, playing a crucial role in HF management by modulating the Wnt1/ß-catenin pathway. Suppression of miR-128 could promote cardiomyocyte proliferation, highlighting the potential value of the miR-128/MDFI interplay in HF treatment.
Assuntos
Apoptose , Cardiomegalia , Proliferação de Células , Insuficiência Cardíaca , MicroRNAs , Miócitos Cardíacos , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Apoptose/genética , Cardiomegalia/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Proliferação de Células/genética , Camundongos , Masculino , Humanos , Via de Sinalização Wnt/genética , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , beta Catenina/metabolismo , beta Catenina/genética , Proteína Wnt1/metabolismo , Proteína Wnt1/genéticaRESUMO
Objective · To evaluate the surgical outcome of RPR composite technique for complex hypertrophic obstructive cardiomyopathy (HOCM). Methods · From June 2009 to December 2015, 9 complex HOCM patients received RPR procedure. There were 6 males and 3 females with age from 22 to 63 years old and the average age of (43±19) years old. Transthorax echocardiography (TTE) showed systolic anterior motion (SAM) and at least moderate mitral valve regurgitation (MR) in all patients before operations. Transesophageal echocardiography (TEE) was used to evaluate the results of procedures during operation. All the patients had been followed up since one week after operation and examined by TTE. Results · All the patients were discharged without complications. Intraoperative TEE indicated that left ventricular outflow tract pressure gradient (LVOTPG) significantly decreased from (92±14) mmHg before operation to (9±3) mmHg after operation (P<0.01). SAM in all the patients disappeared. One week after operation, TTE demonstrated remarkable reduction in the thickness of ventricular septum, LVOTPG and MR than those before operation (P<0.01). Mean follow-up was 26 months. All the patients became asymptomatic. LVOTPG remained low and MR remained mild. There were no deaths, reoperations, or any other adverse consequences. Conclusion · RPR technique is an effective surgical method to relieve LVOTO and MR of complex HOCM to lead a better life.